Zf9, a Kruppel-like transcription factor up-regulated
            <i>in vivo</i>
            during early hepatic fibrosis

Ratziu, Vlad; Lalazar, Avraham; Wong, Lu-Min; Dang, Qi; Collins, Colin C.; Shaulian, Eitan; Jensen, Susan E.; Friedman, Scott L.

doi:10.1073/pnas.95.16.9500

Cited by 228 publications

(208 citation statements)

References 38 publications

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“…28 In rat HSC, KLF6 is rapidly induced in response to liver injury and participates in the regulation of genes associated with the fibrogenic phenotype of HSC. 29 Based on these observations, HSP47 expression by HSC might be predicted to be regulated in an activation-dependent manner. The available data do not confirm this prediction and suggest that the transcriptional regulation of HSP47 by HSC may differ from that of 3T3 cells.…”

Section: Discussionmentioning

confidence: 99%

Expression of HSP47, a collagen-specific chaperone, in normal and diseased human liver

Brown

Broadhurst

Mathahs

et al. 2005

Laboratory Investigation

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HSP47 is a collagen-specific chaperone that is required for normal collagen synthesis. In animal models of liver injury, hepatic stellate cells (HSC) have been identified as a source of HSP47. Because expression of HSP47 has not been investigated in human liver, the aim of these studies was to characterize expression of HSP47 in human liver and to investigate its regulation in human HSC in vitro. Immunohistochemistry demonstrated staining for HSP47 along the sinusoids of normal and cirrhotic human livers and in fibrous septa. Dual fluorescence confocal microscopy showed colocalization of HSP47 with synaptophysin, a marker for HSC. Levels of immunoreactive HSP47 and its transcript tended to be higher in cirrhotic livers than in normal livers. The abundance of HSP47 protein was unchanged by treatment of cultured human HSC with TGF-b1, angiotensin II, hypoxia and a number of other treatments intended to increase collagen synthesis. A modest reduction in HSP47 was achieved by transfection with antisense oligonucleotides and was associated with a significant decrease in procollagen synthesis. These observations suggest that HSP47 is constitutively expressed in human HSC and that HSP47 may be a target for antifibrotic therapy.

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Section: Discussionmentioning

confidence: 99%

Expression of HSP47, a collagen-specific chaperone, in normal and diseased human liver

Brown

Broadhurst

Mathahs

et al. 2005

Laboratory Investigation

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“…Measurement of proliferation was determined by assaying 3 H-thymidine incorporation into DNA as described previously. 6 …”

Section: Methodsmentioning

confidence: 99%

“…Krüppel-like factor 6 (KLF6), a ubiquitously expressed zinc finger transcription factor, 6 has been identified as a tumor suppressor gene in prostate, 7,8 colon, 9 and nasopharyngeal 10 cancers, as well as astrocytic gliomas. 11 Moreover, downregulation of KLF6 messenger RNA levels has been described in lung 12,13 and esophageal 14 cancers, the latter also being associated with promoter methylation.…”

mentioning

confidence: 99%

Frequent inactivation of the tumor suppressor Kruppel-like factor 6 ( KLF6 ) in hepatocellular carcinoma

et al. 2004

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Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, reflecting incomplete characterization of underlying mechanisms and lack of early detection. Krüppel-like factor 6 (KLF6) is a ubiquitously expressed zinc finger transcription factor that is deregulated in multiple cancers through loss of heterozygosity (LOH) and/or inactivating somatic mutation. We analyzed the potential role of the KLF6 tumor suppressor gene in 41 patients who had HCC associated with hepatitis C virus (16 patients), hepatitis B virus (12 patients, one of whom was coinfected with hepatitis C virus), and other etiologies (14 patients) by determining the presence of LOH and mutations. Overall, LOH and/or mutations were present in 20 (49%) of 41 tumors. LOH of the KLF6 gene locus was present in 39% of primary HCCs, and the mutational frequency was 15%. LOH and/or mutations were distributed across all etiologies of HCC evaluated, including patients who did not have cirrhosis. Functionally, wild-type KLF6 decreased cellular proliferation of HepG2 cells, while patient-derived mutants did not. In conclusion, we propose that KLF6 is deregulated by loss and/or mutation in HCC, and its inactivation may contribute to pathogenesis in a significant number of these tumors.

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“…We focused our present studies on the Kru Èppel-like zinc ®nger transcription factors (Ruppert et al 1988) which are a subset of the abundantly found DNA-binding C 2 H 2 -type zinc ®nger factors in eukaryotes (Klug & Schwabe 1995). Exempli®ed by the factors Sp1 (Dynan & Tjian 1983) and GBF (Suzuki et al 1998) (also known as CPBP (Koritschoner et al 1997) and Zf9 (Ratziu et al 1998) but hereafter referred to as GBF), they often bind GC-rich sequences with similar sequence-speci®c binding properties (Sogawa et al 1993;T. Suzuki & M. Horikoshi, unpublished results).…”

Section: Introductionmentioning

confidence: 99%

Regulation of interaction of the acetyltransferase region of p300 and the DNA‐binding domain of Sp1 on and through DNA binding

et al. 2000

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Background: The coactivator p300 acts as a transcriptional adaptor for many DNA-binding activators. The ®nding that p300 possesses intrinsic acetyltransferase activity which, by chemically modifying histone tails affects the nucleosomal environment and transcription, has greatly advanced our understanding of its function. Subsequent recent studies have shown that non-histone proteins are also acetylated. However, one central question which has remained unanswered is how the coactivator/ acetyltransferase interacts with DNA-binding activators to modulate their actions.

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Zf9, a Kruppel-like transcription factor up-regulated in vivo during early hepatic fibrosis

Abstract: ABSTRACT

Cited by 228 publications

References 38 publications

Expression of HSP47, a collagen-specific chaperone, in normal and diseased human liver

Expression of HSP47, a collagen-specific chaperone, in normal and diseased human liver

Frequent inactivation of the tumor suppressor Kruppel-like factor 6 ( KLF6 ) in hepatocellular carcinoma

Regulation of interaction of the acetyltransferase region of p300 and the DNA‐binding domain of Sp1 on and through DNA binding

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